Why methamphetamine is so addictive and damaging to brain

Washington, October 15 : A study has cast new light on why the drug methamphetamine is very addictive and damaging to the brain.

Scientists at the U.S. Department of Energy's (DOE) Brookhaven National Laboratory used positron emission tomography (PET) to track tracer doses of methamphetamine in humans' brains, and found that the addictive and long-lasting effects of the drug were partially due to its pharmacokinetics, the rate at which it enters and clears the brain, and its distribution.

The study involved 19 healthy, non-drug-abusing volunteers, and included a comparison with cocaine.

The study, published in the journal Neuroimage, also looked for differences by race.

"Methamphetamine is one of the most addictive and neurotoxic drugs of abuse. It produces large increases in dopamine, a brain chemical associated with feelings of pleasure and reward - both by increasing dopamine's release from nerve cells and by blocking its reuptake," said Brookhaven chemist Joanna Fowler, lead author on the study.

While it is known that drugs that produce greater elevations in brain dopamine tend to be more addictive, other factors-like the speed with which a drug enters and clears the brain, and its distribution within the brain-can also be important in determining its addictive and toxic potential.

The researchers said that they also wanted to determine whether there were any differences between Caucasians and African Americans.

"Reports that the rate of methamphetamine abuse among African Americans is lower than for Caucasians led us to question whether biological or pharmacokinetic differences might explain this difference," Fowler said.

During the study, the researchers measured brain uptake, distribution, and clearance of methamphetamine by injecting 19 normal healthy men (9 Caucasian, 10 African American) with a radioactively tagged form of the drug in "trace" doses too small to have any psychoactive effects.

The team used PET scanning cameras to monitor the concentration and distribution of the tagged methamphetamine in the subjects' brains.

On the same day, the same subjects were injected with trace doses of cocaine, and scanned for comparison.

The researchers also measured the availability of dopamine reuptake proteins, known as dopamine transporters, in each research subject's brain.

Analyzing the PET scans, the researchers observed that methamphetamine binds all over the brain and stays a long time, while cocaine binds only in the striatum (the reward center) and leaves the brain quickly.

Just like cocaine, methamphetamine entered the brain quickly, a finding consistent with both drugs' highly reinforcing effects. However, methamphetamine lingered in the brain significantly longer than cocaine.

While cocaine was concentrated only in the 'reward' center and cleared rapidly, methamphetamine was concentrated all over the brain, where it remained throughout the study.

"This slow clearance of methamphetamine from such widespread brain regions may help explain why the drug has such long-lasting behavioral and neurotoxic effects," Fowler said.

The researchers also observed significant differences in cocaine pharmacokinetics between African Americans and Caucasians, with the African Americans exhibiting higher uptake of cocaine, a later rise to peak levels, and slower clearance.

However, the scientists did not find any differences in methamphetamine pharmacokinetics between those groups.

"This suggests that variables other than pharmacokinetics and bioavailability account for the lower prevalence of methamphetamine abuse in African Americans. The differences observed for cocaine pharmacokinetics are surprising considering there are no differences in cocaine abuse prevalence between these two ethnic groups," Fowler said.

These differences may merit further study, and also suggest the need to match subjects by ethnic group in future studies to avoid interference from this potentially confounding variable.